miR-130 Suppresses Adipogenesis by Inhibiting Peroxisome Proliferator-Activated Receptor γ Expression

Abstract

Adipose tissue development is tightly regulated by altering gene expression. MicroRNAs are strong posttranscriptional regulators of mammalian differentiation. We hypothesized that microRNAs might influence human adipogenesis by targeting specific adipogenic factors. We identified microRNAs that showed varying abundance during the differentiation of human preadipocytes into adipocytes. Among them, miR-130 strongly affected adipocyte differentiation, as overexpressing miR-130 impaired adipogenesis and reducing miR-130 enhanced adipogenesis. A key effector of miR-130 actions was the protein peroxisome proliferator-activated receptor γ (PPARγ), a major regulator of adipogenesis. Interestingly, miR-130 potently repressed PPARγ expression by targeting both the PPARγ mRNA coding and 3′ untranslated regions. Adipose tissue from obese women contained significantly lower miR-130 and higher PPARγ mRNA levels than that from nonobese women. Our findings reveal that miR-130 reduces adipogenesis by repressing PPARγ biosynthesis and suggest that perturbations in this regulation is linked to human obesity.

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ACKNOWLEDGMENTS

We thank Stephen R. Farmer for advice and insight into this study.

This research was funded by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, by grants DK46200, DK072488, DK080448, and DK052398 (to S.K.F. and M.J.L.) and by grant DK072476 (to S.R.S.).

We indicate no potential conflicts of interest.